1. Field of the Invention
The present invention relates to immunotherapeutic methods for treating autoimmune disorders. In particular, this invention is directed to methods for treating autoimmune disorders by administering antibodies that bind to a B-cell antigen, such as the CD22, CD20, CD19, and CD74 or HLA-DR antigen. The antibodies are administered alone or in combination, and may be naked or conjugated to a drug, toxin or therapeutic radioisotope. Bispecific antibody fusion proteins which bind to the B-cell antigens can be used according to the present invention, including hybrid antibodies which bind to more than one B-cell antigen. The present invention also is directed to multimodal therapeutic methods in which the antibody administration is supplemented by administration of other therapeutic modalities.
2. Background
Antibodies against the CD20 antigen have been investigated for the therapy of B-cell lymphomas. For example, a chimeric anti-CD20 antibody, designated as “IDEC-C2B8,” has activity against B-cell lymphomas when provided as unconjugated antibodies at repeated injections of doses exceeding 500 mg per injection. Maloney et al., Blood 84:2457 (1994); Longo, Curr. Opin. Oncol. 8:353 (1996). About 50 percent of non-Hodgkin's patients, having the low-grade indolent form, treated with this regimen showed responses. Therapeutic responses have also been obtained using 131I-labeled B1 anti-CD-20 murine monoclonal antibody when provided as repeated doses exceeding 600 mg per injection. Kaminski et al., N. Engl. J. Med. 329:459 (1993); Press et al., N. Engl. J. Med. 329:1219 (1993); Press et al., Lancet 346:336 (1995). However, these antibodies, whether provided as unconjugated forms or radiolabeled forms, have shown only modest activity in patients with the more prevalent and lethal form of B-cell lymphoma, the intermediate or aggressive type.
Autoimmune diseases are a class of diseases associated with a B-cell disorder. Examples include immune-mediated thrombocytopenias, such as acute idiopathic thrombocytopenic purpura and chronic idiopathic thrombocytopenic purpura, myasthenia gravis, lupus nephritis, lupus erythematosus, and rheumatoid arthritis. The most common treatments are corticosteroids and cytotoxic drugs, which can be very toxic. These drugs also suppress the entire immune system, can result in serious infection, and have adverse affects on the liver and kidneys. Other therapeutics that have been used to treat Class III autoimmune diseases to date have been directed against T-cells and macrophages. A need remains for more effective methods of treating autoimmune diseases, particularly Class III autoimmune diseases.